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Compound inhibits one critical pathway in breast cancer growth

le ability to inhibit Stat3 activity, more than any of the other 99 compounds that we tested," Lin said.

The researchers then used STA-21 to treat several types of cells, including human breast cancer cell lines with constantly activated Stat3 as well as those without, and also normal human skin fibroblasts, cells that make up connective tissue. Stat3 isn't constantly activated in fibroblasts, and these cells were used as a control.

After exposure to STA-21, breast cancer cells with constantly active Stat3 were dying. However, STA-21 had a minimal effect on breast tumor cells that didn't express constantly activated Stat3, nor did it have an adverse effect on the normal fibroblasts.

"Many types of cancer cells express constantly activated Stat3 and seem to depend on it for survival," he continued. "When we blocked that constantly activated Stat3 pathway, the cells died."

STA-21 is derived from a family of antibiotics but is not currently used as an antibiotic. The STA-21 molecule is small enough to enter a cell, and can be delivered directly to cancer cells or to a solid tumor.

Also, shutting down one of the key survival mechanisms in a cancer cell may help increase the effectiveness of chemotherapy and also lessen the toxicity of treatment, Lin said.

"Using a compound that inhibits the constantly activated Stat3 pathway may make tumor cells more sensitive to chemotherapy," Lin said.

He and his colleagues will continue to study the effects of STA-21 and related compounds, or analogs, in different types of cancer cells.

"An analog of STA-21 could work even better," he said. "We may be able to create one that can be even more effective and less toxic to normal cells."


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Contact: Jiayuh Lin
linj@ccri.net
614-355-2652
Ohio State University
7-Mar-2005


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